chr1-161548496-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000569.8(FCGR3A):c.244G>A(p.Asp82Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 8 hom., cov: 37)

Exomes 𝑓: 0.00084 ( 36 hom. )

Failed GnomAD Quality Control

Consequence

FCGR3A
NM_000569.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.79

Publications

21 publications found

Variant links:

Genes affected

FCGR3A (HGNC:3619): (Fc gamma receptor IIIa) This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. This gene (FCGR3A) is highly similar to another nearby gene (FCGR3B) located on chromosome 1. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, whereas FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. Mutations in this gene are associated with immunodeficiency 20, and have been linked to susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

FCGR3A Gene-Disease associations (from GenCC):

autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FCGR3A links:

ENSG00000289768 (HGNC:):

ENSG00000289768 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.066061705).

BP6

Variant 1-161548496-C-T is Benign according to our data. Variant chr1-161548496-C-T is described in ClinVar as Benign. ClinVar VariationId is 3910128.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3A	NM_000569.8 link	c.244G>A	p.Asp82Asn	missense_variant	Exon 3 of 5	ENST00000443193.6	NP_000560.7	P08637

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3A	ENST00000443193.6 link	c.244G>A	p.Asp82Asn	missense_variant	Exon 3 of 5	1	NM_000569.8	ENSP00000392047.2		P08637
ENSG00000289768	ENST00000699402.1 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 3 of 4			ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1181

AN:

120458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00388

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.00690

Gnomad EAS

AF:

0.00540

Gnomad SAS

AF:

0.00965

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0150

Gnomad NFE

AF:

0.00557

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.000670

AC:

162

AN:

241658

AF XY:

0.000558

show subpopulations

Gnomad AFR exome

AF:

0.00753

Gnomad AMR exome

AF:

0.000238

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000519

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000840

AC:

1096

AN:

1304062

Hom.:

Cov.:

134

AF XY:

0.000758

AC XY:

493

AN XY:

650218

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0111

AC:

350

AN:

31528

American (AMR)

AF:

0.000440

AC:

AN:

43184

Ashkenazi Jewish (ASJ)

AF:

0.000354

AC:

AN:

22598

East Asian (EAS)

AF:

0.000210

AC:

AN:

38006

South Asian (SAS)

AF:

0.000530

AC:

AN:

81114

European-Finnish (FIN)

AF:

0.000220

AC:

AN:

50032

Middle Eastern (MID)

AF:

0.00117

AC:

AN:

5118

European-Non Finnish (NFE)

AF:

0.000600

AC:

587

AN:

978808

Other (OTH)

AF:

0.00119

AC:

AN:

53674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

119

238

358

477

596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00980

AC:

1182

AN:

120566

Hom.:

Cov.:

AF XY:

0.00991

AC XY:

587

AN XY:

59260

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0174

AC:

615

AN:

35358

American (AMR)

AF:

0.00647

AC:

AN:

12374

Ashkenazi Jewish (ASJ)

AF:

0.00690

AC:

AN:

2462

East Asian (EAS)

AF:

0.00542

AC:

AN:

4430

South Asian (SAS)

AF:

0.00913

AC:

AN:

3834

European-Finnish (FIN)

AF:

0.0126

AC:

AN:

7788

Middle Eastern (MID)

AF:

0.0163

AC:

AN:

184

European-Non Finnish (NFE)

AF:

0.00557

AC:

288

AN:

51744

Other (OTH)

AF:

0.0117

AC:

AN:

1618

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.293

Heterozygous variant carriers

124

248

372

496

620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0636

Hom.:

ExAC

AF:

0.00141

AC:

171

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0010

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.014

.;T;T;T;.;.;.

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.13

T;.;.;T;T;T;T

MetaRNN

Benign

0.066

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.065

.;N;N;N;.;.;.

PhyloP100

-3.8

PrimateAI

Benign

0.27

PROVEAN

Benign

1.6

.;.;N;N;.;.;N

REVEL

Benign

0.013

Sift

Benign

1.0

.;.;T;T;.;.;T

Sift4G

Benign

1.0

.;T;T;T;.;.;.

Polyphen

0.0

.;B;B;B;.;.;.

Vest4

0.11

MVP

0.18

MPC

0.13

ClinPred

0.015

GERP RS

-8.8

Varity_R

0.10

gMVP

0.22

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over